Abstract

Background

Fatty acids are essential dietary nutrients, and one of their important roles is providing
polyunsaturated fatty acids (PUFAs) for the growth and function of nervous tissue.
Short chain fatty acids (SCFAs) are a group of compounds derived from the host microbiome
that were recently linked to effects on the gut, the brain, and behavior. They are
therefore linked to neurodevelopmental disorders such as autism. Reduced levels of
PUFAs are associated with impairments in cognitive and behavioral performance, which
are particularly important during brain development. Recent studies suggest that omega
-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
are involved in neurogenesis, neurotransmission, and protection from oxidative stress.
Omega-3 PUFAs mediate some of these effects by antagonizing Omega-6 PUFA (arachidonic
acid, AA)-induced proinflammatory prostaglandin E₂ (PGE₂) formation.

Methods

In this work, the absolute and relative concentrations of propionic (PPA), butyric
and acetic acids, as well as PUFAs and their precursors (α-Linolenic and linoleic),
were measured in the brain tissue of PPA-neurointoxicated rat pups (receiving 250 mg
PPA/Kg body weight for 3 consecutive days) as a rodent model with persistent autistic
features compared with healthy controls.

Results

The data revealed remarkably lower levels of omega6/omega3, α-Linolenic/Linoleic,
α-Linolenic/EPA, α-Linolenic/DHA, EPA/DHA, and AA/Linoleic acid ratios in PPA-intoxicated
rats. The role of these impaired ratios is discussed in relation to the activity of
desaturases and elongases, which are the two enzymatic groups involved in the synthesis
of PUFAs from their precursors. The relationship between the abnormal relative concentrations
of the studied fatty acids and oxidative stress, neurotransmission, and neuroinflammation
is also discussed in detail.

Conclusions

This study demonstrates that fatty acid ratios are useful for understanding the mechanism
of PPA neurotoxicity in a rodent model of autism. Therefore, it is possible to use
these ratios for predictions in patients with this disorder.